Functional Effects of IGF2BP2 Genetic Variants on Growth Traits in Sheep

ABSTRACT Growth traits are economically important in sheep, but the regulatory variants contributing to body‐weight variation remain incompletely characterized. A selective‐sweep analysis identified a candidate region on chromosome 1 containing IGF2BP2 . Sequence comparison indicated that IGF2BP2 is highly conserved across mammals. Genotyping of Hu sheep, Hulunbuir sheep, and Tan sheep identified Chr1 g.202274996G>A was significantly associated with sheep body weight at 6 months of age. Epigenomic data indicated that the region containing this variant has features of an active cis‐regulatory element, and dual‐luciferase assays showed that the A allele reduced enhancer activity relative to the G allele. In isogenic sheep fetal fibroblast clones generated by cytosine base editing, the AA genotype was associated with lower IGF2BP2 and CCAR1 expression than the GG genotype. MeRIP‐qPCR further indicated genotype‐dependent differences in m 6 A‐enriched CCAR1 RNA. Together, these findings support Chr1 g.202274996G>A as a candidate regulatory variant affecting IGF2BP2 expression and body weight in Hu sheep, and provide a potential molecular marker for the genetic improvement of growth traits in sheep.